Uncovering Genetic Interactions: CRISPR-Mediated Gene Knockouts and Activations in Understanding Complex Diseases
DOI:
https://doi.org/10.31580/pjmls.v7isp2.3164Keywords:
Activation, Anticancer, CRISPR/Cas9, Epistasis, Knock out, Neurological disorders, Personalized medicine, Polygenic disordersAbstract
Complex diseases involve intricate genetic interactions that are difficult to study with traditional methods. CRISPR gene editing provides a powerful tool for dissecting these interactions and advancing therapeutic strategies. This article discusses how CRISPR-mediated gene editing can be used to discover genetic interactions related to composite diseases and how targeted genetic on/off strategies offer nice therapeutic prospects. The Pub Med and Genomics Online data was analyzed from 2010 to 2023 in this systematic review which followed the PRISMA guidelines and included only research articles. The 80 papers' criteria for CRISPR-based genetic interaction analysis consisted of both experimental data on gene knockout and activation of genes and the pathways’ outcomes in the context of multifactorial diseases, including cancer, neurodegenerative disorders, and metabolic syndromes. Studies were excluded from further consideration if they provided insufficient or irrelevant experimental evidence regarding complex gene interactions, lacked clear methodological rigour, or focused on non-relevant disease models. The exclusion of these studies refined the dataset, ensuring a higher quality of evidence and minimizing potential biases in the analysis. This improved the reliability of conclusions drawn regarding the role of CRISPR in studying multifactorial diseases. 40 studies were reviewed for depth analysis of which 15 were analyzed in the summarized table. It showed that the mechanism performs well in explaining important gene-to-gene relations with actual gene knockouts being typically compensated. Activation studies exemplified improved comprehension of genetic networks controlling pathogenic processes as well as cancer and neurological disorders. CRISPR-based genetic interventions and CRISPRKO/CRISPR on are valuable techniques to dissect pathophysiological progressions and genetic interacting networks in multiple diseases. It opens up a door to develop new gene-targeted medicine and helps in the understanding of precision medicine.
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